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Electroacupuncture may alleviate diabetic neuropathic pain by inhibiting the microglia P2X4R and neuroinflammation

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Abstract

Diabetic neuropathic pain (DNP) is a common and destructive complication of diabetes mellitus. The discovery of effective therapeutic methods for DNP is vitally imperative because of the lack of effective treatments. Although 2 Hz electroacupuncture (EA) was a successful approach for relieving DNP, the mechanism underlying the effect of EA on DNP is still poorly understood. Here, we established a rat model of DNP that was induced by streptozotocin (STZ) injection. P2X4R was upregulated in the spinal cord after STZ-injection. The upregulation of P2X4R was mainly expressed on activated microglia. Intrathecal injection of a P2X4R antagonist or microglia inhibitor attenuated STZ-induced nociceptive thermal hyperalgesia and reduced the overexpression of brain-derived neurotrophic factor (BDNF), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the spinal cord. We also assessed the effects of EA treatment on the pain hypersensitivities of DNP rats, and further investigated the possible mechanism underlying the analgesic effect of EA. EA relieved the hyperalgesia of DNP. In terms of mechanism, EA reduced the upregulation of P2X4R on activated microglia and decreased BDNF, IL-1β and TNF-α in the spinal cord. Mechanistic research of EA's analgesic impact would be beneficial in ensuring its prospective therapeutic effect on DNP as well as in extending EA's applicability.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This research was supported by the National Natural Science Foundation of China (81804181 to X.F.H. and 81774389 to Y.L.J.), the Natural Science Foundation of Zhejiang Province of China (LY22H270006 to Y.L.J.), the Research Fund for Zhejiang Traditional Chinese Medicine University Affiliated Hospital (2022FSYYZZ09 to Y.L.J.), and the Key Laboratory of Acupuncture and Neurology of Zhejiang Province (2019E10011).

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  1. Si-ying Qu, Han-zhi Wang and Qun-qi Hu contributed equally to this work as co-first authors.

Authors and Affiliations

  1. Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Si-ying Qu, Han-zhi Wang, Qun-qi Hu, Yi-qi Ma, Yu-rong Kang, Li-qian Ma, Xiang Li, Lu-hang Chen, Bo-yu Liu, Xiao-mei Shao, Bo-yi Liu, Jun-ying Du, Yi Liang, Yong-liang Jiang, Jian-qiao Fang & Xiao-fen He

  2. Department of TCM Gynecology, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University, Hangzhou, 310000, China

    Han-zhi Wang & Hong-li Zhao

  3. Key Laboratory of Acupuncture and Neurology of Zhejiang Province, Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China

    Bo-yu Liu, Xiao-mei Shao, Bo-yi Liu, Jun-ying Du, Yi Liang, Yong-liang Jiang, Jian-qiao Fang & Xiao-fen He

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Contributions

X.H., J.F. and Y.J. conceived and designed the experiments. S.Q., H.W., Q.H., Y.K., X.L., L.C. and L.M. performed animal experiments. Q.H., Y.M., and L.M. performed western blotting experiments. S.Q. and H.W. performed immunofluorescence labeling experiments. B.L. and H.Z. performed data analysis. X.H., S.Q. and H.W. wrote the manuscript. X.S., Y.L., J.D. and B.L. performed revising. All authors reviewed and revised this manuscript and reviewed the final version of the manuscript.

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Correspondence to Yong-liang Jiang, Jian-qiao Fang or Xiao-fen He.

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This study was permitted by The Animal Welfare Committee of Zhejiang Chinese Medical University (Approval number: IACUC-20190805-04). The institution agreed to participate and agreed to publish.

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Qu, Sy., Wang, Hz., Hu, Qq. et al. Electroacupuncture may alleviate diabetic neuropathic pain by inhibiting the microglia P2X4R and neuroinflammation. Purinergic Signalling (2023). https://doi.org/10.1007/s11302-023-09972-9

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